This project continues to be directed toward the development, validation, and application of methods for,measurement of physiological and biochemical processes in functional and structural regions of the nervous system in animals and man. The methods are first developed for use in animals with quantitative autoradiography and then adapted for use in man with PET. The [14C]iodoantipyrine ([14C]IAP) method for measuring local cerebral blood flow (ICBF) and the [14C]deoxyglucose ([14C]DG) method for measuring local cerebral glucose utilization (ICMRgtc) are examples of methods that were developed in this program; adaptations of these methods are currently the only generally accepted quantitative methods routinely used in man with PET. These methods are applied to various physiological, pharmacological, and pathological states. Some of the major efforts in this project during the past year were as follows: l) model development and evaluation to simplify and to improve the accuracy and reliability of the [18F]fluorodeoxyglucose ([18F]FDG) adaptation of the (14C]DG method for human use with PET; 2) studies of the effects of stress produced by interference of glucose metabolism on local blood flow in the brain; 3) effects of hibernation on local cerebral blood flow and glucose utilization in the hibernating ground squirrel; 4) studies of the neurogenic control of the cerebral circulation; 5) development of a method to facilitate the determination of needed parameters to adapt the deoxyglucose method for use in pathological tissues and pathophysiological conditions; 6) studies of the role of nitric oxide in the coupling of cerebral blood flow to local cerebral energy metabolism and/or functional activity (described separately in another project report, 1.e., #02590-03).